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The preference signature of the SARS-CoV-2 Nucleocapsid NTD for its 5’-genomic RNA elements

The nucleocapsid protein (N) of SARS-CoV-2 plays a pivotal role during the viral life cycle. It is involved in RNA transcription and accounts for packaging of the large genome into virus particles. N manages the enigmatic balance of bulk RNA-coating versus precise RNA-binding to designated cis-regul...

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Autores principales: Korn, Sophie Marianne, Dhamotharan, Karthikeyan, Jeffries, Cy M., Schlundt, Andreas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10246530/
https://www.ncbi.nlm.nih.gov/pubmed/37286558
http://dx.doi.org/10.1038/s41467-023-38882-y
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author Korn, Sophie Marianne
Dhamotharan, Karthikeyan
Jeffries, Cy M.
Schlundt, Andreas
author_facet Korn, Sophie Marianne
Dhamotharan, Karthikeyan
Jeffries, Cy M.
Schlundt, Andreas
author_sort Korn, Sophie Marianne
collection PubMed
description The nucleocapsid protein (N) of SARS-CoV-2 plays a pivotal role during the viral life cycle. It is involved in RNA transcription and accounts for packaging of the large genome into virus particles. N manages the enigmatic balance of bulk RNA-coating versus precise RNA-binding to designated cis-regulatory elements. Numerous studies report the involvement of its disordered segments in non-selective RNA-recognition, but how N organizes the inevitable recognition of specific motifs remains unanswered. We here use NMR spectroscopy to systematically analyze the interactions of N’s N-terminal RNA-binding domain (NTD) with individual cis RNA elements clustering in the SARS-CoV-2 regulatory 5’-genomic end. Supported by broad solution-based biophysical data, we unravel the NTD RNA-binding preferences in the natural genome context. We show that the domain’s flexible regions read the intrinsic signature of preferred RNA elements for selective and stable complex formation within the large pool of available motifs.
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spelling pubmed-102465302023-06-08 The preference signature of the SARS-CoV-2 Nucleocapsid NTD for its 5’-genomic RNA elements Korn, Sophie Marianne Dhamotharan, Karthikeyan Jeffries, Cy M. Schlundt, Andreas Nat Commun Article The nucleocapsid protein (N) of SARS-CoV-2 plays a pivotal role during the viral life cycle. It is involved in RNA transcription and accounts for packaging of the large genome into virus particles. N manages the enigmatic balance of bulk RNA-coating versus precise RNA-binding to designated cis-regulatory elements. Numerous studies report the involvement of its disordered segments in non-selective RNA-recognition, but how N organizes the inevitable recognition of specific motifs remains unanswered. We here use NMR spectroscopy to systematically analyze the interactions of N’s N-terminal RNA-binding domain (NTD) with individual cis RNA elements clustering in the SARS-CoV-2 regulatory 5’-genomic end. Supported by broad solution-based biophysical data, we unravel the NTD RNA-binding preferences in the natural genome context. We show that the domain’s flexible regions read the intrinsic signature of preferred RNA elements for selective and stable complex formation within the large pool of available motifs. Nature Publishing Group UK 2023-06-07 /pmc/articles/PMC10246530/ /pubmed/37286558 http://dx.doi.org/10.1038/s41467-023-38882-y Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Korn, Sophie Marianne
Dhamotharan, Karthikeyan
Jeffries, Cy M.
Schlundt, Andreas
The preference signature of the SARS-CoV-2 Nucleocapsid NTD for its 5’-genomic RNA elements
title The preference signature of the SARS-CoV-2 Nucleocapsid NTD for its 5’-genomic RNA elements
title_full The preference signature of the SARS-CoV-2 Nucleocapsid NTD for its 5’-genomic RNA elements
title_fullStr The preference signature of the SARS-CoV-2 Nucleocapsid NTD for its 5’-genomic RNA elements
title_full_unstemmed The preference signature of the SARS-CoV-2 Nucleocapsid NTD for its 5’-genomic RNA elements
title_short The preference signature of the SARS-CoV-2 Nucleocapsid NTD for its 5’-genomic RNA elements
title_sort preference signature of the sars-cov-2 nucleocapsid ntd for its 5’-genomic rna elements
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10246530/
https://www.ncbi.nlm.nih.gov/pubmed/37286558
http://dx.doi.org/10.1038/s41467-023-38882-y
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